Data analysis is continuing in a case-control study of risk factors for the acute leukemias in adults in which patients can be classified according to clonal chromosome characteristics, immunologic phenotype, and other biochemical markers. A total of 658 primary leukemia patients who were enrolled in cancer treatment protocols sponsored by Cancer and Leukemia group B, a cooperative cancer study group, and 636 population controls were interviewed regarding exposure to solvents and chemicals, smoking, irradiation, use of potentially toxic medications, and family medical history. An additional 250 AML patients and 90 myelodysplasia patients were also interviewed for related studies. Living within 5 miles of a factory was found to be associated with a 40% increase in risk for AML and 70% increase in risk for ALL. Although specific industries appeared to be more strongly associated with leukemia risk than others, no individual hazards were identified. There was a 2-fold risk for leukemia associated with smoking among individuals age 60 and over, among whom smoking could be estimated to account for 30% of leukemia risk. Associations varied with morphology and with cytogenetics, suggesting that examining discrete disease subtypes permit more accurate assessment of risk. Similarly a strong association between occupational exposures and ras gene activation in AML underscores the importance of identifying homogeneous subgroups of patients. Evaluation of ras mutations in 250 additional AML patients is being completed in order to confirm the association between ras and chemical exposure. Additional analyses are focusing on hair dyes and marijuana, both of which appear to be associated with increased risk, and on medical history and use of specific medications. Occupational exposure data are being reviewed and reclassified in order to link specific classes of chemical exposure with potential risk for leukemia subtypes.